Cycle multistability and synchronization mechanisms in coupled interneurons: In-phase and anti-phase dynamics under current stimuli

Over the last decade, high-frequency oscillations (HFOs), very high-frequency oscillations (VHFOs), and ultra-fast oscillations (UFOs) have been proposed as possible biomarkers for epileptogenic zones in individuals with drug-resistant epilepsy. Despite considerable interest, the mechanisms responsible for producing such high frequencies, significantly surpassing the physiological limits of neuronal firing, remain an open question. Using concepts from bifurcation theory, we extend our mathematical framework for modeling the emergence of apparent VHFOs, which might eventually manifest in depth electroencephalographic (EEG) signals, by incorporating an external stimulus responsible for subsequent frequency multiplication. Focusing on the dynamics of two gap-junctionally coupled interneurons, this research provides a detailed analysis of multistable regions, along with an extensive description of possible dynamical regimes associated with external current stimulation, analogous to the frequency-input curve for a single interneuron. In particular, we describe the ability of the stimulus to activate and deactivate oscillation modes in anti-phase or in-phase, including their mutual interchange. Finally, we apply this framework to analyze a collective response of a large heterogeneous two-layer network.